The objective of our proposed research will be to elucidate the central nervous system pathways and neurotransmitters in these pathways controlling parasympathetic outflow to the gastrointestinal tract in the cat. This will be done by determining; (1) the effect of exciting hindbrain nuclei containing cell bodies of preganglionic vagal fibers (dorsal motor nucleus of the vagus, nucleus ambiguus, nucleus tractus solitarius, external cyneate nucleus) on gastrointestinal motility and secretion, (2) the anatomical connection between these nuclei and the gastrointestinal tract, (3) which of these nuclei contain vagal fibers that mediate reflex-induced changes in motility and secretion, (4) the anatomical connection between the brain and the sacral parasympathetic nucleus, (5) the anatomical connections between brain areas known to affect gastrointestinal function (hypothalamus, amygdala) and incoming afferent into the brain (nucleus tractus solitarius) as well as hinddrain nuclei representing the final path for vagal outflow to the gut, and (6) the neurotransmitters and/or neuromodulators that permit communication between neurons in the identified pathways. Methods to be used include measuring GI motility with strain gage transducers and gastric acid and pepsin secretion, retrograde and antegrade neuroanatomical mapping, electrical stimulation and electrolytic lesioning, and cerebroventricular perfusion and microinjection of putative neurotransmitters (e.g. GABA, TRH, serotonin, gastrin, opoid peptides, cholecystokinin) and antagonists to these neurotransmitters. The results obtained from these studies should provide new insight into: (1) neural determiniants of gastric secretion which might evolve as causative factors for either peptic disease or disease characterized by diminished acid secretion, and (2) neural determinants of intestinal motility which might evolve as causative factors for irritable bowel syndrome. The results obtained should also pinpoint sites where drugs can act through the nervous system to correct derangements in gastrointestinal function.